Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

Effect of treatment willingness on specialist assessment and treatment uptake for hepatitis C virus infection among people who use drugs: the ETHOS study.

Among people who inject drugs (PWID) with chronic HCV, the association between HCV treatment willingness and intent, and HCV specialist assessment and treatment were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort. Recruitment was through six opioid substitution treatment clinics, two community health centres and one Aboriginal community controlled health organisation in Australia. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 67% were 'definitely willing' to receive HCV treatment and 70% reported plans to initiate therapy 12 months postenrolment. Those definitely willing to receive HCV treatment were more likely to undergo specialist assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001), compared to those with lower treatment willingness. Those with early HCV treatment plans were more likely to undergo specialist assessment (65% vs 27%, P < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without early plans. In adjusted analyses, HCV treatment willingness independently predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI 2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment willingness was high and predicted specialist assessment and treatment. Strategies for enhanced HCV care should be developed with an initial focus on people willing to receive treatment and to increase treatment willingness among those less willing.

Indoor solar thermal energy saving time with phase change material in a horizontal shell and finned-tube heat exchanger.

An experimental as well as numerical investigation was conducted on the melting/solidification processes of a stationary phase change material (PCM) in a shell around a finned-tube heat exchanger system. The PCM was stored in the horizontal annular space between a shell and finned-tube where distilled water was employed as the heat transfer fluid (HTF). The focus of this study was on the behavior of PCM for storage (charging or melting) and removal (discharging or solidification), as well as the effect of flow rate on the charged and discharged solar thermal energy. The impact of the Reynolds number was determined and the results were compared with each other to reveal the changes in amount of stored thermal energy with the variation of heat transfer fluid flow rates. The results showed that, by increasing the Reynolds number from 1000 to 2000, the total melting time decreases by 58%. The process of solidification also will speed up with increasing Reynolds number in the discharging process. The results also indicated that the fluctuation of gradient temperature decreased and became smooth with increasing Reynolds number. As a result, by increasing the Reynolds number in the charging process, the theoretical efficiency rises.

Lower life expectancy among people with an HCV notification: a population-based linkage study.

Among people with hepatitis C virus (HCV) infection, liver disease-related deaths have risen over the last 20 years. Life expectancy has not been estimated in this population. HCV notifications (mandatory notification of anti-HCV-positive serology since 1991) reported to the New South Wales Health Department from 1992 to 2006 were linked to cause of death data. Abridged life tables were constructed from age-specific mortality rates. Life expectancy from ages 18-70 years for non-drug-related mortality causes was estimated using competing risk methods and compared to the general population of Australia. The cohort comprised 81 644 individuals with an HCV notification, with median follow-up of 7.6 years. Median age at notification was 34 years [interquartile range (IQR) 28-42] and 63% were male. Between 1992 and 2006, 4607 deaths occurred. Median age at liver- and drug-related death among males was 51 (IQR 45-66) and 36 (IQR 31-42) years, respectively, and among females was 63 (IQR 49-74) and 36 (IQR 30-41) years, respectively. In each year of follow-up before 2000, 15-21% of deaths were liver- and 30-39% were drug-related. After 2000, liver-related deaths increased to 20-26% of deaths in each year and drug-related deaths decreased to 13-19%. Excluding drug-related causes of death, life expectancy was lowered by an average of 4.2 (SD ± 1.0) and 5.4 (SD ± 0.7) years for males and females, respectively. Among people with an HCV notification, an increasing proportion of deaths are liver-related. Following removal of drug-related mortality, life expectancy in this population remained considerably lower, compared with the general population.

Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice.

The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner mitochondrial membranes, has been studied in many cell types, but only a few studies have been conducted on adult differentiated tissues such as cardiac or skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could play different roles, especially in response to an environmental stress like exercise. Endurance exercise increases energy demand in skeletal muscle and repeated activity induces mitochondrial biogenesis and activation of fusion-fission cycles for the synthesis of new mitochondria. But currently no study has clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse model of haploinsufficiency for the Opa1 gene (Opa1(+/-)), we therefore studied the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles to endurance exercise training. Our results show that, surprisingly, Opa1(+/-) mice were able to perform the same physical activity as control mice. However, the adaptation strategies of both strains after training differed: while in control mice mitochondrial biogenesis was increased as expected, in Opa1(+/-) mice this process was blunted. Instead, training in Opa1(+/-) mice led to an increase in endurance capacity, and a specific adaptive response involving a metabolic remodelling towards enhanced fatty acid utilization. In conclusion, OPA1 appears necessary for the normal adaptive response and mitochondrial biogenesis of skeletal muscle to training. This work opens new perspectives on the role of mitochondrial dynamics in skeletal muscle cells and during adaptation to stress.

An overview of biofilm and its detection in clinical samples.

In many instances, wound colonising-bacteria are thought to be capable of forming biofilms, a significant factor contributing to delays or failure in wound healing. This review summarises the accumulated knowledge of biofilm and addresses the unmet need of biofilm detection in clinical wound samples.

EFFECTIVE DOSE ESTIMATION IN WHOLE BODY 18F-FDG PET/CT IMAGING.

Positron emission tomography-computed tomography (PET-CT) with internal administration of the FDG-18 is characterized as a widespread functional imaging modality in diagnostic radiation medicine, which increases the patient effective doses owing to the presence of internal and external radiation sources. Hence, patient effective dose estimation has been pinpointed as a significant factor in radiation protection assessment. A large number of studies have been published in this regard, and various dosimetry methods have been surveyed. According to our previous research, 10 patients had participated in PET-CT scans with three static time sequences imaging. PET effective doses were estimated using a simple method derived from Anderson et al. and Kaushik et al. coefficients, and the CT effective doses were surveyed with a CTDI phantom and cylindrical ionization chamber. The CT dose was tripled owing to the three static time-sequences imaging. The effective doses were calculated using different coefficients and the results of the PET effective doses were compared. The PET-CT effective dose was varied from 17.14 to 18.42 mSv based on Kaushik et al. coefficients which were measured for one low-dose CT scan. This study aimed to survey simple PET-CT effective dose estimation using three static-time imaging approaches which increases the total patient effective doses.

Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.

BACKGROUND: Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. RESULTS: Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. CONCLUSION: Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract.

Identification of a heparin-binding hemagglutinin present in mycobacteria.

Adherence to mammalian host tissues is an important virulence trait in microbial pathogenesis, yet little is known about the adherence mechanisms of mycobacteria. Here, we show that binding of mycobacteria to epithelial cells but not to macrophages can be specifically inhibited by sulfated carbohydrates. Using heparin-Sepharose chromatography, a 28-kD heparin-binding protein was purified from culture supernatants and cell extracts of Mycobacterium bovis and Mycobacterium tuberculosis. This protein, designated heparin-binding hemagglutinin (HBHA), promotes the agglutination of rabbit erythrocytes, which is specifically inhibited by sulfated carbohydrates. HBHA also induce mycobacterial aggregation, suggesting that it can mediate bacteria-bacteria interactions as well. Hemagglutination, mycobacterial aggregation, as well as attachment to epithelial cells are specifically inhibited in the presence of anti-HBHA antibodies. Immunoelectron microscopy using anti-HBHA monoclonal antibodies revealed that the protein is surface exposed, consistent with a role in adherence. Immunoblot analyses using antigen-specific antibodies indicated that HBHA is different from the fibronectin-binding proteins of the antigen 85 complex and p55, and comparison of the NH2-terminal amino acid sequence of purified HBHA with the protein sequence data bases did not reveal any significant similarity with other known proteins. Sera from tuberculosis patients but not from healthy individuals were found to recognize HBHA, indicating its immunogenicity in humans during mycobacterial infections. Identification of putative mycobacterial adhesins, such as the one described in this report, may provide the basis for the development of new therapeutic and prophylactic strategies against mycobacterial diseases.

Genomic rearrangements in OPA1 are frequent in patients with autosomal dominant optic atrophy.

INTRODUCTION: Autosomal dominant optic atrophy (ADOA) is considered as the most common form of hereditary optic neuropathy. Although genetic linkage studies point to the OPA1 locus on chromosome 3q28-q29 as by far the most common gene locus, previous screening studies-based on sequencing of the coding exons-detected OPA1 mutations in only 32-70% of ADOA patients. We therefore hypothesised that larger deletions or duplications that remained undetected in previous screening approaches may substantially contribute to the prevalence of OPA1 mutations in ADOA. METHODS: 42 independent ADOA patients were analysed for the presence of genomic rearrangements in OPA1 by means of multiplex ligation probe amplification (MLPA). Deletions or duplications were confirmed either by long distance polymerase chain reaction (PCR) and breakpoint sequencing or loss of heterozygosity analyses with flanking microsatellite markers. Patients underwent ophthalmological examination including visual acuity, colour vision testings, perimetry and funduscopy. RESULTS: We identified genomic rearrangements in 8 of 42 patients, including single exon deletions of exon 9 and exon 24, respectively, a deletion of exons 1-5, two different deletions of the complete OPA1 gene as well as a duplication of the exons 7-9, with the latter being present in three unrelated families. Patients' phenotypes were highly variable, similar to patients with point mutation in OPA1. DISCUSSION: Our findings show that gross genomic aberrations at the OPA1 gene locus are frequent in ADOA and substantially contribute to the spectrum and prevalence of OPA1 mutations in ADOA patients. They further strengthen the hypothesis that haploinsufficiency is a major pathomechanism in OPA1 associated ADOA.

Resistance carrying plasmid in a traumatic wound.

OBJECTIVE: To isolate and identify antibiotic-resistant bacteria from the exudate of a complex wound and determine if antibiotic resistance genes are chromosomal or plasmid borne. METHOD: Antibiotic resistant bacteria from wound exudate of a single clinical sample were selected on agar media with ampicillin. A single colony was further screened for resistance to kanamycin by antibiotic-supplemented agar and to other antibiotics by an automated Phoenix instrument. Identification of the isolate was carried out by biochemical profiling and by 16S rDNA analysis. RESULTS: Approximately 51% of total bacteria in the wound exudate with identical colony morphotype were resistant to 100 microg/ml of ampicillin. A single colony from this population also demonstrated resistance to 50 microg/ml of kanamycin on kanamycin-supplemented agar. Further antimicrobial sensitivity testing by the Phoenix instrument indicated resistance to inhibitory concentrations of amoxicillin-clavulanate, ampicillin-sulbactam, cefazolin, gentamicin, nitrofurantoin, tobramycin, and trimethoprim-sulfamethoxazole. Biochemical and 16S rDNA analysis identified this bacterial isolate as a member of genus Enterobacter. A plasmid preparation from this isolate successfully transferred ampicillin and kanamycin resistance to E. coli competent cells. E. coli transformants displayed two resistance phenotypes and the plasmids from these transformants displayed two different restriction type patterns, with one correlating to ampicillin and kanamycin resistance and the other only to ampicillin resistance. CONCLUSION: A multiple antibiotic-resistant Enterobacter spp. from the wound fluid of a clinical sample was found to carry an antibiotic-resistant plasmid in a closely related species E. coli. The presence of antibiotic resistance plasmid in Enterobacteria that are part of the normal microbial flora of the human gut and skin could lead to the spread of resistance phenotype and emergence of antibiotic resistant pathogens. This study suggests normal human microbial fl ora could be a potential reservoir for resistance genes.

Effect of magnesium sulfate on extubation time and acute pain in coronary artery bypass surgery.

BACKGROUND: Post-operative pain control is one of the greatest concerns for both physicians and patients. In this study, the effect of magnesium sulfate (MgSO(4)) solution infusion on post-operative pain scores and extubation time in patients undergoing elective coronary artery bypass graft (CABG) surgeries was assessed. METHODS: In a double-blind, randomized, placebo-controlled clinical trial, 218 patients scheduled for elective CABG were selected and randomly assigned to two groups. After matching inclusion and exclusion criteria for the patients, intravenous MgSO(4) was administered intraoperatively for one group and placebo to the second group. Except for this, all the cases were similar regarding anesthesia and surgery. RESULTS: The MgSO(4) patients were extubated sooner compared with the placebo group. Pain scores reported by the group who received MgSO(4) were less at the 6th, 12th, 18th and 24th hours after the operation; also, they needed less morphine sulfate during this period. CONCLUSION: The results demonstrated a significantly shortened post-operative time for extubation and reduced acute post-operative pain scores by intravenous MgSO(4) infusion during elective CABG surgery.

Evaluation of Blood Parameters Alteration Following Low-dose Radiation Induced by Myocardial Perfusion Imaging.

INTRODUCTION: With increasing the usage of myocardial perfusion imaging (MPI) for the diagnosis of ischemic heart disease, we aimed to evaluate the side effects of low-dose radiation induced by this technique on blood elements, especially proteins and liver function factors. MATERIAL AND METHODS: 40 eligible patients (Mean age: 54.62±10.35, 22 female and 18 male), who had referred to the nuclear medicine department for MPI from May till August 2014, were enrolled in the study. A blood sample was taken from each patient just before and 24 hours after the injection of 740Mbq of Tecnetium-99m Methoxy isobutyl isonitrile (99mTc-MIBI) in the rest phase of the MPI in a reference medical laboratory; blood tests included total protein (TP), albumin (Alb), globulin (Glo), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), direct bilirubin (D.Bili), total bilirubin (T.Bili), serum iron (SI), total iron bounding capacity (TIBC), Albumin globulin ratioA/G ratio), and complete blood count (CBC). RESULTS: Injection of 740Mbq99mTc-MIBI caused a significant increase in serum levels of AST (p= 0.001), ALT (p= 0.001), SI (p= 0.030), TIBC (p= 0.003) and A/G Ratio (p= 0.020). However, following radiotracer injection, a significant decrease was noted in the serum levels of TP (p= 0.002), Alb (p= 0.014), Glo(p= 0.002), ALP (p= 0.001), D.Bili (p= 0.003) and T.Bili (p= 0.000). CONCLUSION: Due to increased usage of MPI, our data highlights the importance of monitoring the clinical and paraclinical effects of the procedure on vital organs and physiological pathways to reduce their adverse effects.

Look Different: Effect of Radiation Hormesis on the Survival Rate of Immunosuppressed Mice.

BACKGROUND: Hormesis is defined as the bio-positive response of something which is bio-negative in high doses. In the present study, the effect of radiation hormesis was evaluated on the survival rate of immunosuppressed BALB/c mice by Cyclosporine A. MATERIAL AND METHODS: We used 75 consanguine, male, BALB/c mice in this experiment. The first group received Technetium-99m and the second group was placed on a sample radioactive soil of Ramsar region (800Bq) for 20 days. The third group was exposed to X-rays and the fourth group was placed on the radioactive soil and then injected Technetium-99m. The last group was the sham irradiated control group. Finally, 30mg Cyclosporine A as the immunosuppressive agent was orally administered to all mice 48 hours after receiving X-rays and Technetium-99m. The mean survival rate of mice in each group was estimated during time. RESULTS: A log rank test was run to determine if there were differences in the survival distribution for different groups and related treatments. According to the results, the survival rate of all pre-irradiated groups was more than the sham irradiated control group (p < .05). The highest survival time was related to the mice which were placed on the radioactive soil of Ramsar region for 20 days and then injected Technetium-99m. CONCLUSION: This study confirmed the presence of hormetic models and the enhancement of survival rate in immunosuppressed BALB/c mice as a consequence of low-dose irradiation. It is also revealed the positive synergetic radioadaptive response on survival rate of immunosuppressed animals.

Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase by endogenous sterol synthesis in cultured intestinal mucosa.

In vitro regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) by compactin, a competitive inhibitor of the enzyme, and mevalonate was studied in rabbit ileum organ culture. Addition of compactin suppressed ileum homogenate reductase activity by over 80% at concentrations up to 0.5 microgram/ml. In contrast, compactin at the same concentrations added to the culture medium induced reductase activity up to 240% of controls. This increase was blocked by cycloheximide and mevalonolactone at 10 mM, but not by mevalonate (salt form) and cholesterol. Similarly, in contrast to ionized mevalonate, mevalonolactone significantly suppressed reductase activity of cultured intestine at 1 and 10 mM by 23 and 62%, respectively. A minor effect was also observed with preformed enzyme in fresh mucosal homogenate. When endogenous cholesterol synthesis was blocked by compactin, mucosal alkaline phosphatase activity decreased progressively, whereas medium activity from desquamated cells did not change. This distribution of the villous cell marker enzyme is characteristic of a decrease in crypt cell renewal and/or villous cell differentiation. This effect of compactin was also reversible with mevalonolactone. The reductase enzyme induced by compactin was probably latent intracellularly, since tissue cholesterol contents dropped sharply after blockade of endogenous sterol synthesis.

Lipoprotein regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured intestinal mucosa.

In vitro regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), was studied in 24-h organ culture of rabbit ileum. Preincubation of mucosal homogenate in phosphate buffer increased apparent reductase activity more than 5-fold. The activation was blocked in the presence of 150 mM NaF, suggesting interconversion of latent reductase by dephosphorylation. No significant further activation was achieved by potato phosphatase treatment. During culture total reductase activity was stimulated by 125% in lipoprotein-free medium. Addition of low density lipoprotein to the medium resulted in a dose-dependent suppression of reductase activity between 0.2 and 1.0 mM lipoprotein cholesterol. At these concentrations LDL inhibition reached 51 and 75% of control, respectively. The reductase response to very low density and high density lipoproteins was biphasic, with a 2- to 3-fold stimulation at 0.1-0.3 mM and a suppression at higher levels. No such stimulation was observed with high density lipoproteins obtained from cholesterol fed animals. Similarly, 'hypercholesterolemic' very low density lipoproteins enhanced reductase activity only slightly. It is concluded that lipoproteins are potent regulators of cholesterol synthesis in cultured intestine.

Type Ia tricuspid atresia with extensive coronary artery abnormalities in a living 22 year old woman.

Type Ia tricuspid atresia, with extensive coronary artery abnormalities, is identified in the oldest living patient with this condition, a 22 year old woman. Clinical characteristics include severe cyanosis, effort dyspnea, myocardial infarction in the past and persistent angina pectoris. "Ideal" pulmonary flow and adequate left ventricular function, despite an akinetic apical segment, are substantive factors for this exceptional longevity. Coronary abnormalities consist of: 1) total proximal occlusion of the left anterior descending coronary artery; and 2) partial diversion of coronary artery flow to a segmental pulmonary artery branch. Nonvisualization of the coronary sinus is also noted. Factors other than atherosclerosis may account for total proximal occlusion of the left anterior descending coronary artery. Survival is threatened by adverse effects of ongoing ischemic coronary events.